Mechanism of Effect of Vagotomy on Pancreatic Secretion. We shall study the effect of vagotomy on protein secretion by transplanted pancreas in response to protein or fat in the intestine. The results of this study should distinguish between interruption of entero-pancreatic reflexes and interference with release of cholecystokinin as the cause of the decrease in protein secretion seen after vagotomy. Trophic Effects of Gastrointestinal Hormones. Using a model that we have developed for rapid production of pancreatic hyperplasia by injection of secretin and cholecystokinin, we shall study the time course of protein, DNA, and RNA synthesis, and of changes produced by starvation, altered diet, or feeding protease inhibitors can be accounted for by hormonal mediation. Structure-Activity Relations of Cholecytoskinin and Gastrin. These two hormones share a common biologically active C-terminal pentapeptide. We shall study progressively longer C-terminal fragments of each hormone to determine the minimal length needed to give the degree of selectivity (for acid secretion in the case of gastric, pancreatic secretion in the case of cholecystokinin) found in the whole molecule. Further Elucidation of the Mechanism by Which Acid Releases Secretin. Since different weak acids have different potencies as stimulants of pancreatic bicarbonate secretion, it has been proposed that the H ion receptor for secretin release may be intracellular and therefore may depend on permeability of unionized acid and on concentration gradients of both protons and unionized acid. We shall test this hypothesis by comparing the potency for stimulation of bicarbonate secrtion of a nonpermeant acid (acidified albumin) and a permeant acid (lactic acid) given at the same pH and the same titratable acid load.